UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived from the research literature.

The UniProt consortium comprises the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB), and the Protein Information Resource (PIR). EBI, located at the Wellcome Trust Genome Campus in Hinxton, UK, hosts a large resource of bioinformatics databases and services. SIB, located in Geneva, Switzerland, maintains the ExPASy (Expert Protein Analysis System) servers that are a central resource for proteomics tools and databases. PIR, hosted by the National Biomedical Research Foundation (NBRF) at the Georgetown University Medical Center in Washington, DC, USA, is heir to the oldest protein sequence database, Margaret Dayhoff's Atlas of Protein Sequence and Structure, first published in 1965.[2] In 2002, EBI, SIB, and PIR joined forces as the UniProt consortium.[3]

Each consortium member is heavily involved in protein database maintenance and annotation. Until recently, EBI and SIB together produced the Swiss-Prot and TrEMBL databases, while PIR produced the Protein Sequence Database (PIR-PSD).[4][5][6] These databases coexisted with differing protein sequence coverage and annotation priorities.

Swiss-Prot was created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and subsequently developed by Rolf Apweiler at the European Bioinformatics Institute.[7][8][9] Swiss-Prot aimed to provide reliable protein sequences associated with a high level of annotation (such as the description of the function of a protein, its domain structure, post-translational modifications, variants, etc.), a minimal level of redundancy and high level of integration with other databases. Recognizing that sequence data were being generated at a pace exceeding Swiss-Prot's ability to keep up, TrEMBL (Translated EMBL Nucleotide Sequence Data Library) was created to provide automated annotations for those proteins not in Swiss-Prot. Meanwhile, PIR maintained the PIR-PSD and related databases, including iProClass, a database of protein sequences and curated families.

The consortium members pooled their overlapping resources and expertise, and launched UniProt in December 2003.[10]

UniProtKB/Swiss-Prot is a manually annotated, non-redundant protein sequence database. It combines information extracted from scientific literature and biocurator-evaluated computational analysis. The aim of UniProtKB/Swiss-Prot is to provide all known relevant information about a particular protein. Annotation is regularly reviewed to keep up with current scientific findings. The manual annotation of an entry involves detailed analysis of the protein sequence and of the scientific literature.[14]

Relevant publications are identified by searching databases such as PubMed. The full text of each paper is read, and information is extracted and added to the entry. Annotation arising from the scientific literature includes, but is not limited to:[10][14][15]

UniProtKB/TrEMBL contains high-quality computationally analyzed records, which are enriched with automatic annotation. It was introduced in response to increased dataflow resulting from genome projects, as the time- and labour-consuming manual annotation process of UniProtKB/Swiss-Prot could not be broadened to include all available protein sequences.[10] The translations of annotated coding sequences in the EMBL-Bank/GenBank/DDBJ nucleotide sequence database are automatically processed and entered in UniProtKB/TrEMBL. UniProtKB/TrEMBL also contains sequences from PDB, and from gene prediction, including Ensembl, RefSeq and CCDS.[16]

UniProt Archive (UniParc) is a comprehensive and non-redundant database, which contains all the protein sequences from the main, publicly available protein sequence databases.[17] Proteins may exist in several different source databases, and in multiple copies in the same database. In order to avoid redundancy, UniParc stores each unique sequence only once. Identical sequences are merged, regardless of whether they are from the same or different species. Each sequence is given a stable and unique identifier (UPI), making it possible to identify the same protein from different source databases. UniParc contains only protein sequences, with no annotation. Database cross-references in UniParc entries allow further information about the protein to be retrieved from the source databases. When sequences in the source databases change, these changes are tracked by UniParc and history of all changes is archived.

The UniProt Reference Clusters (UniRef) consist of three databases of clustered sets of protein sequences from UniProtKB and selected UniParc records.[18] The UniRef100 database combines identical sequences and sequence fragments (from any organism) into a single UniRef entry. The sequence of a representative protein, the accession numbers of all the merged entries and links to the corresponding UniProtKB and UniParc records are displayed. UniRef100 sequences are clustered using the CD-HIT algorithm to build UniRef90 and UniRef50.[18][19] Each cluster is composed of sequences that have at least 90% or 50% sequence identity, respectively, to the longest sequence. Clustering sequences significantly reduces database size, enabling faster sequence searches.